The human kallikrein gene family is a group of genes that are clustered on chromosome 19q13.3-q13.4 and share significant homologies at both the nucleotide and amino acid levels (1-5). Until recently, this family was thought to contain only three genes, including KLK1 (encoding for human kallikrein 1, hK1; also known as pancreaticrenal kallikrein), KLK2 (encoding for human kallikrein 2, hK2) and KLK3 (encoding for human kallikrein 3, hK3; also known as prostate-specific antigen, PSA). Over the last 2-3 years, new genes were identified in the same chromosomal region and are now considered to be members of the kallikrein gene family (6). These new kallikrein genes are currently known with various empirical names. An international group of investigators has recently agreed on new human kallikrein gene nomenclature (7). This gene family now contains at least 15 genes which are designated KLK1 . . . KLK15, while their encoded proteins are designated as hK1 . . . hK15.
The normal epithelial cell-specific 1 (NES1) gene is one of these newly identified genes. With the new nomenclature, NES1 is designated as KLK10 and the encoded protein as hK10. KLK10 was isolated with subtractive hybridization, between radiation-transformed and non-transformed breast epithelial cells (8). KLK10 resides on chromosome 19q13.4, spans about 5.5 kb of genomic DNA sequence and contains six exons (one untranslated) and five introns (9). hK10 is a secreted serine protease and its amino acid sequence has 35-40% identity and 50-55% similarity with other members of the human kallikrein gene fly, including PSA. The physiological function of hK10 has not as yet been elucidated. Since the KLK10 gene is down-regulated in breast cancer cell lines, it is considered to play a role in the regulation of normal cell growth. Goyal et al. have recently suggested that KLK10 may encode for a tumor suppressor gene (10). When the KLK10 gene was transfected into the tumorigenic breast cancer cell line MDA-MB-231, its anchorage-independent growth was reduced and when this cell line was inoculated into nude mice, tumor formation was significantly decreased.
Ovarian cancer is a serious disease which causes more deaths than any other cancer of the female reproductive system (13). Since survival could be dramatically improved if the disease is diagnosed early (14), there is great interest in the identification of biomarkers that could aid in the early detection and facilitate grading and/or staging (15). Unfortunately, the current serological markers for ovarian carcinoma, including CA125 (16-19), inhibin (20-23), OVX1 (24) as well as many other markers (reviewed in 25) have shown some promise but have not gained wide clinical acceptance. Another potential ovarian cancer marker, lysophosphatidicacid appears to also have some value for this purpose (26).
There is an urgent need for discovery and validation of new serum biomarkers for ovarian carcinoma. Early diagnosis of ovarian cancer with serological analysis may improve clinical outcomes through administration of effective treatment.